《生命科学》 2018, 30(11): 1202-1209

精子RNA及RNA修饰在获得性遗传中的研究进展

张云芳1，2，3，张　莹1，陈　琦2*，段恩奎1*

(1 中国科学院动物研究所干细胞与生殖生物学国家重点实验室，北京 100101；2 美国内华达大学雷诺医学院，内华达州 89503；3 中国人民解放军陆军军医大学新桥医院血液科，重庆 400037)

摘　要：摘　要：越来越多的证据表明，上一代在环境压力下产生的某些获得性性状可以“记忆”在配子中，并以一种不依赖DNA 序列的方式传递给下一代，这种现象被称为获得性遗传。然而，关于精子中介导获得性遗传现象的分子机制尚不清楚。近年来，随着精子RNA 领域的发展，我们实验室率先发现精子中一类来源于成熟tRNA 的小RNA (tRNA-derived small RNAs， tsRNAs) 及其RNA 修饰可以作为一种新型的表观遗传信息载体，介导父代获得性代谢紊乱性状向子代传递。此外，我们进一步发现了调控精子RNA 介导获得性遗传的关键分子——tRNA 甲基转移酶DNMT2，从RNA 修饰及修饰酶的角度为获得性遗传的机制研究打开了新思路。鉴于该领域的迅速发展，该文拟从精子tsRNAs、RNA 修饰以及DNMT2 的角度综述近年来精子RNA 及RNA 修饰介导的获得性遗传机制的研究进展。

Advance in sperm RNA and RNA modification mediated epigenetic inheritance

ZHANG Yun-Fang1，2，3， ZHANG Ying1， CHEN Qi2*， DUAN En-Kui1*

(1 State Key Laboratory of Stem Cell and Reproduction Biology， Chinese Academy of Science， Beijing 100101， China; 2 University of Nevada， Reno School of Medicine， NV 89503， USA; 3 Department of Hematology， Xinqiao Hospital， Army Medical University， Chongqing 400037， China)

Abstract: Abstract: Increasing evidence showed that parental environment exposure can be stored and transmitted to the next generation by germ cells in a DNA-sequence independent manner， which was known as acquired epigenetic inheritance. However， the underlying molecular mechanism is still unclear. Our recent work firstly revealed that sperm tRNA derived small RNAs (tsRNAs)， along with their RNA modifications， could act as an ‘epigenetic information carrier’， to deliver paternal acquired metabolic disorders to the offspring. Following this clue， we further found that a tRNA m5C methyltransferase， Dnmt2， was a key regulator of sperm RNA mediated epigenetic inheritance， which suggested a new direction for future studies of the underling molecular mechanisms. Due to the rapid development of this hot field， here we provided an overall view on sperm tsRNA and RNA modifications， along with the discovery of Dnmt2， in mediating paternally acquired epigenetic inheritance.